| Paralogue | Variant | Associated Disease | Mapping Quality | Consensus | Pubmed |
|---|---|---|---|---|---|
| RYR1 | I4938T | Malignant hyperthermia | High | 9 | 19191329 |
| RYR1 | I4938M | Central core disease | High | 9 | 14985404 |
To assess whether the paralogue annotation here confidently predicts that variation at this residue is pathogenic, it is important to check the reports in the Pubmed links above to ascertain that the mutations in these paralogues have been proved likely to be disease-causing. It is also important to check that the direction of effect of the variant in the paralogue is compatible with your observed phenotype in RYR2.
| RYR2 | DEYEIYRIIFDITFFFFVIVILLAIIQGLI>I<DAFGELRDQQEQVKEDMETKCFICGIGNDY | 4897 |
| RYR1 | DEYELYRVVFDITFFFFVIVILLAIIQGLI>I<DAFGELRDQQEQVKEDMETKCFICGIGSDY | 4968 |
| RYR3 | DPYEMYRIVFDITFFFFVIVILLAIIQGLI>I<DAFGELRDQQEQVREDMETKCFICGIGNDY | 4800 |
| cons | > < |
| Protein | CDS | Disease Classification | Disease | dbSNP links | Effect Prediction |
|---|---|---|---|---|---|
| p.I4867M | c.14601T>G | Inherited Arrhythmia | CPVT | SIFT: deleterious Polyphen: benign | |
| Reports | Inherited Arrhythmia | CPVT | Clinical and molecular characterization of patients with catecholaminergic polymorphic ventricular tachycardia. Circulation. 2002 106(1):69-74. 12093772 | ||
| Inherited Arrhythmia | CPVT | Enhanced store overload-induced Ca2+ release and channel sensitivity to luminal Ca2+ activation are common defects of RyR2 mutations linked to ventricular tachycardia and sudden death. Circ Res. 2005 97(11):1173-81. 16239587 | |||
| Inherited Arrhythmia | CPVT | New exome data question the pathogenicity of genetic variants previously associated with catecholaminergic polymorphic ventricular tachycardia. Circ Cardiovasc Genet. 2013 6(5):481-9. doi: 10.1161/CIRCGENETICS.113.000118. 24025405 | |||
| p.I4867V | c.14599A>G | Inherited Arrhythmia | CPVT | SIFT: Polyphen: | |
| Reports | Inherited Arrhythmia | CPVT | Familial cardiological and targeted genetic evaluation: low yield in sudden unexplained death and high yield in unexplained cardiac arrest syndromes. Heart Rhythm. 2013 10(11):1653-60. doi: 10.1016/j.hrthm.2013.08.022. 23973953 | ||